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Stem-Cell Therapy/Platelet-Rich Plasma for Orthopedic Applications and ​Platelet-Rich Plasma/Platelet-Derived Growth Factor for Wound Healing and Other Miscellaneous Non-Orthopedic Conditions
MA07.008d

Policy

​ORTHOPEDIC APPLICATIONS

STEM-CELL THERAPY
Stem-cell therapy, alone or in combination with platelet-derived products (e.g., plasma, lysate), for all orthopedic applications is considered experimental/investigational and, therefore, not covered, because the safety and/or effectiveness of these services cannot be established by review of the available published peer-reviewed literature. This includes, but is not limited to, the following conditions/procedures:

  • Cartilage defect repair
  • Joint fusion​
  • Meniscal tissue repair/regeneration
  • Osteonecrosis​
​PLATELET-RICH PLASMA
Autologous platelet-rich plasma (PRP) for the treatment of all orthopedic conditions is considered experimental/investigational and, therefore, not covered, because the safety and/or effectiveness of these services cannot be established by review of the available published peer-reviewed literature. This includes, but is not limited to, the following conditions/procedures:​

  • Primary use (injection) for the following conditions:
    • ​Achilles tendinopathy
    • Lateral epicondylitis​​
    • Osteoarthritis​
    • Osteochondral lesions​
    • Plantar fasciitis
  • Adjunctive use in the following surgical procedures:
    • Anterior cruciate ligament reconstruction​
    • Hip fracture​ repair
    • Long-bone nonunion repair
    • Patellar tendon repair
    • Rotator cuff repair
    • Spinal fusion
    • Subacromial decompression surgery​
    • Total knee arthroplasty​ 
WOUND HEALING AND OTHER MISCELLANEOUS NON-ORTHOPEDIC CONDITIONS

​​PLATELET-RICH PLASMA​
Medically Necessary

Autologous PRP for the treatment of chronic non-healing diabetic wounds is considered medically necessary and, therefore, covered​ for a duration of 20 weeks, when prepared by devices whose FDA-approved indications include the management of exuding cutaneous wounds, such as diabetic ulcers.

​Not Covered

​Autologous PRP for the treatment of chronic non-healing diabetic wounds beyond 20 weeks is not covered by the company because it is a service not covered by Medicare. Therefore, it is not eligible for reimbursement consideration​.

​Experimental/Investigational

Autologous PRP for the treatment of all other chronic non-healing wounds is considered experimental/investigational and, therefore, not covered, because the safety and/or effectiveness of these services cannot be established by review of the available published peer-reviewed literature.​

Autologous PRP for the treatment of acute surgical wounds when the autologous PRP is applied directly to the closed incision, or for dehiscent wounds​, is considered experimental/investigational and, therefore, not covered, because the safety and/or effectiveness of these services cannot be established by review of the available published peer-reviewed literature.

PLATELET-DERIVED GROWTH FACTOR
Autologous platelet-derived growth factor (PDGF) for the treatment of chronic, non-healing cutaneous wounds is considered experimental/investigational and, therefore, not covered, because the safety and/or effectiveness of these services cannot be established by review of the available published peer-reviewed literature.

RECOMBINANT PLATELET-DERIVED GROWTH FACTOR (BECAPLERMIN)
Recombinant PDGF​ (i.e., Becaplermin) for the treatment of chronic, non-healing subcutaneous wounds is considered experimental/investigational and, therefore, not covered, because the safety and/or effectiveness of these services cannot be established by review of the available published peer-reviewed literature.

Guidelines

This policy is consistent with Medicare’s coverage determination. The Company’s payment methodology may differ from Medicare.

BENEFIT APPLICATION

​​​​Subject to the terms and conditions of the applicable Evidence of Coverage, stem cell therapy for all orthopedic applications is not eligible for payment under the medical benefits of the Company’s Medicare Advantage products because the service is considered experimental/investigational and, therefore, not covered. ​

Subject to the terms and conditions of the applicable Evidence of Coverage, autologous platelet-rich plasma (PRP) for the treatment of chronic non-healing diabetic wounds for a duration of 20 weeks is covered under the medical benefits of the Company's Medicare Advantage products when the medical necessity criteria listed in this medical policy are met. However, the following uses for autologous PRP have been identified in this policy as experimental/investigational and are, therefore, not eligible for coverage or reimbursement by the Company:

  • acute surgical wounds when the autologous PRP is applied directly to the closed incision, or for dehiscent wounds​, and
  • all orthopedic applications.
Subject to the applicable Evidence of Coverage, autologous PRP for the treatment of chronic non-healing diabetic wounds beyond 20 weeks​ is not eligible for payment under the medical benefits of the Company’s Medicare Advantage products because the service is considered not covered.

Subject to the terms and conditions of the applicable Evidence of Coverage, autologous platelet-derived growth factor (PDGF) for the treatment of chronic, non-healing cutaneous wounds is not eligible for payment under the medical benefits of the Company’s Medicare Advantage products because the services are considered experimental/investigational and, therefore, not covered.​

Subject to the terms and conditions of the applicable Evidence of Coverage, recombinant PDGF (i.e., Becaplermin) for the treatment of chronic, non-healing subcutaneous wounds​ is​ not eligible for payment under the medical benefits of the Company’s Medicare Advantage products because the services are considered experimental/investigational and, therefore, not covered.​

Services that are experimental/investigational are excluded for the Company’s Medicare Advantage products. Therefore, they are not eligible for reimbursement consideration.

​US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

The U.S. Food and Drug Administration (FDA) regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation, Title 21, parts 1270 and 1271. Mesenchymal stem cells, platelet-rich plasma, and platelet-derived growth factor are included in these regulations.

MESENCHYMAL STEM CELLS (MSCs)
Concentrated autologous MSCs do not require approval​ by the FDA. No products using engineered or expanded MSCs have been approved by the FDA for orthopedic applications.​ 

PLATELET-RICH PLASMA (PRP)/PLATELET-DERIVED GROWTH FACTOR (PDGF)
Although blood products such as PRP/PDGF do not follow the traditional FDA regulatory pathway, numerous PRP/PDGF preparation systems have been cleared for marketing by the FDA through the 510(k) process. These systems produce platelet-rich preparations intended to be mixed with bone graft materials to enhance the bone grafting properties in orthopedic practices. The use of PRP/PDGF outside of this setting (e.g., an office injection) would be considered off-label. The Aurix System (previously called AutoloGel; Cytomedix) and SafeBlood (SafeBlood Technologies) are two related but distinct autologous blood-derived preparations that can be used at the bedside for immediate application. Both AutoloGel and SafeBlood have been specifically marketed for wound healing. Other devices may be used during surgery (e.g., Medtronic Electromedics, Elmd-500 Autotransfusion system, the Plasma Saver device, the SmartPReP [Harvest Technologies] device). The Magellan Autologous Platelet Separator System (Medtronic Sofamor Danek) includes a disposable kit for use with the Magellan Autologous Platelet Separator portable tabletop centrifuge. GPSII (BioMet Biologics), a gravitational platelet separation system, was cleared for marketing by the FDA through the 510(k) process for use as disposable separation tube for centrifugation and a dual cannula tip to mix the platelets and thrombin at the surgical site. Filtration or plasmapheresis may also be used to produce platelet-rich concentrates. The use of different devices and procedures can lead to variable concentrations of activated platelets and associated proteins, increasing variability between studies of clinical efficacy.​

RECOMBINANT PLATELET-DERIVED GROWTH FACTOR (BECAPLERMIN; REGRANEX GEL)
Becaplermin (Regranex gel; Smith & Nephew) was approved by the FDA in 1997, and has the following labeled indication:

​"REGRANEX gel is indicated for the treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply, when used as an adjunct to, and not a substitute for, good ulcer care practices including initial sharp debridement, pressure relief and infection control."

 Furthermore, Regranex (becaplermin) gel has the following limitations for use:

  • The efficacy of Regranex gel has not been established for the treatment of pressure ulcers and venous stasis ulcers and has not been evaluated for the treatment of diabetic neuropathic ulcers that do not extend through the dermis into subcutaneous tissue (Stage I or II) or ischemic diabetic ulcers.
  • The effects of Regranex gel on exposed joints, tendons, ligaments, and bone has not been established in humans.
  • Regranex gel should not be used in wounds that close by primary intention.
Individuals are typically treated with becaplermin once a day for up to 20 weeks or until completely healed. Application of becaplermin may be performed by the individual in the home. Becaplermin is available in 2-, 7.5-, and 15-g tubes and is applied in a thin continuous layer, about 1/16 of an inch thick. The amount of becaplermin used will depend on the size of the ulcer, measured in square centimeters. However, an average-sized ulcer, measuring 3 cm2, treated for an average length of time of 85 days, will require a little more than one 15-g tube. If the ulcer is treated for the maximum length of time of 140 days, 1.75 of the  15-g tubes would be required.​

​In 2008, Smith & Nephew added the following black box warning to the labeling for Regranex: “An increased rate of mortality secondary to malignancy was observed in patients treated with 3 or more tubes of Regranex Gel in a postmarketing retrospective cohort study. Regranex Gel should only be used when the benefits can be expected to outweigh the risks. Regranex Gel should be used with caution in patients with known malignancy.” In 2018, the “Boxed Warning” and “Warnings and Precautions” were changed to remove “increased rate of cancer mortality” and “cancer mortality,” respectively.​

Description

STEM-CELL THERAPY FOR ORTHOPEDIC APPLICATIONS

Mesenchymal stem cells (MSCs) are multipotent stem cells (also referred to as stromal multipotent cells) that are able to differentiate into a variety of tissue types, including organs, trabecular bones, tendons, articular cartilage, ligaments, muscles, fats, and various musculoskeletal tissues. MSCs have possible orthopedic applications, which include the treatment of damaged bones, cartilage, ligaments, tendons, and intervertebral discs.

MSCs decrease as people age, and acute and chronic illnesses and diseases can tax stem-cell reserves. MSCs can be increased and stem-cell reserves replenished by treatment with drugs such as filgrastim injection (Neupogen®) and plerixafor injection (Mozobil®) to mobilize stem cells, or by autologous stem-cell transplantation. Although MSCs can be harvested from the bone marrow, harvesting requires an additional procedure that may result in donor site morbidity.

Tissues such as muscle, cartilage, tendon, ligaments, and vertebral discs show limited capacity for endogenous repair (i.e., the repair of cells within their own structures). Therefore, tissue engineering techniques have been developed to improve the efficiency of repair or regeneration of damaged musculoskeletal tissues. Using an engineered process to induce cell division and differentiation, without adverse effects such as the formation of neoplasms, remains a challenge.

According to the US Food and Drug Administration (FDA), "...Cell-based therapy is one of the most rapidly advancing approaches intended to repair, replace, restore, or regenerate cells, tissues, and organs. The cell-based therapies use immature stem cells that are expanded outside the body. The expanded cells are sometimes used in their immature state, but are often manufactured into mature cells before being used. Manufacturing a large number of cells outside the natural environment of the body may lead to ineffective or dangerous cells. It is important to control the production process and to define measures that reliably predict safety and efficacy of the cell-based products."

No products using engineered MSCs have been approved by the FDA for orthopedic applications. The FDA has determined that MSCs sold by Regenerative Sciences for use in the Regenexx™ Procedure (Regenerative Sciences, Colorado) would be considered drugs or biological products and thus require submission for a New Drug Application (NDA) or a Biologics Licensing Application (BLA) to the FDA. These procedures by Regenexx™ have platelet-derived components as well.

The evidence base evaluating stem cell therapy for cartilage defects, meniscal defects, joint fusion procedures, or osteonecrosis includes small randomized controlled trials (RCTs) and nonrandomized comparative trials. Reported outcomes include symptoms, morbid events, functional outcomes, quality of life, and treatment-related morbidity. The use of stem cells for orthepedic conditions is an on going area of research with several clinical trials in progress, but are not expected to be completed for several years. Studies have used MSCs from bone marrow, adipose tissue, and peripheral blood. Overall, the quality of evidence is low and there is a possibility of publication bias. The strongest evidence to date is on MSCs expanded from bone marrow, which includes several phase 1 or 2 RCTs. However, limitations in these studies prevent reaching a conclusion, but the results do support future study in phase 3 trials. A smaller number of studies evaluated alternative methods of obtaining MSCs with mixed results. Larger, long-term studies are needed to evaluate the efficacy and safety of these procedures. Overall, there is a lack of evidence that clinical outcomes are improved. The evidence is insufficient to determine that the technology results in an improvement in the net health outcomes, therefore the use of stem cells for orthopedic applications is considered experimental/investigational.

In a 2020 guideline from American Association of Orthopaedic Surgeons (AAOS) on the management of glenohumeral joint osteoarthritis (OA) states that injectable biologics such as stem cells cannot be recommended in the treatment glenohumeral joint OA. There was consensus from the panel that better standardization and high-quality evidence from clinical trials is needed to provide definitive evidence on the efficacy of biologics in glenohumeral OA. The strength of evidence was rated as no reliable scientific evidence to determine benefits and harms.

In a 2019 guideline from the American College of Rheumatology and Arthritis Foundation (Kolasinski​ SL et al. 2020) on osteoarthritis (OA) of the hand, hip, and knee gave a strong recommendation against stem cell injections in patients with knee and/or hip OA, noting the heterogeneity in preparations and lack of standardization of techniques. No recommendation was made for hand OA, since efficacy of stem cells has not been evaluated.​

PLATELET-RICH PLASMA​ (PRP) FOR ORTHOPEDIC APPLICATIONS​

PRIMARY TREATMENT FOR TENDINOPATHIES
The evidence base evaluating the use of PRP for the treatment of tendinopathy includes multiple randomized controlled trials (RCTs) (Gupta PK et al. 2020; Scott A et al. 2019; Fitzpatrick J et al. 2019; Martin JI et al. 2019) and systematic reviews with meta-analyses (Johal H et al. 2019; Miller LE et al. 2017; Tsikopoulos K et al. 2016; Balasubramaniam U​ et al. 2015; Andia I et al. 2014). Relevant reported outcomes include symptoms, functional outcomes, health status measures, quality of life, and treatment-related morbidity. The majority of the more recently-published systematic reviews and meta-analyses that only included RCTs failed to show a statistically and/or clinically significant impact on symptoms (e.g., pain) or functional outcomes. Although one systematic review found statistically significantly lower pain scores at 12 months with PRP versus the comparators, its results should be interpreted with caution due to important study limitations. Compared to a corticosteroid injection, two RCTs (Gupta PK et al. 2020; Fitzpatrick J et al. 2019) found PRP to result in significantly improved pain scores, important relevancy gaps and study limitations exist that prevent reaching strong conclusions based on this evidence. Additionally, compared to placebo, PRP did not significantly improve pain after 12 months (Scott A et al. 2019). Finally, compared with lidocaine, in individuals receiving PRP as an adjunct to ultrasound-guided tenotomy for recalcitrant elbow tendinopathy, there were no significant differences in pain or disability outcomes (Martin JI et al. 2019​).

​​In 2013, the National Institute for Health and Care Excellence (NICE) issued guidance on the use of autologous blood injection for tendinopathy. The guideline concluded that the current evidence on the safety and efficacy of autologous blood injection for tendinopathy was “inadequate” in quantity and quality.

PRIMARY TREATMENT FOR NON-TENDON SOFT TISSUE INJURY OR INFLAMMATION
The evidence base evaluating the use of PRP for the treatment of non-tendon soft tissue injury or inflammation (e.g., plantar fasciitis) includes several small RCTs (Tabrizi A​ et al. 2020; Peerbooms JC et al. 2019; Shetty SH et al. 2019; Johnson-Lynn S et al. 2019; Monto RR​ 2014​)​, multiple prospective observational studies, and a systematic review (Franceschi F et al. 2014). There are no large double-blind RCTs of sufficient duration (i.e., 2 years) to demonstrate efficacy. ​Relevant reported outcomes include symptoms, functional outcomes, health status measures, quality of life, and treatment-related morbidity. The systematic review identified three RCTs on PRP for plantar fasciitis, however the authors did not pool study findings. In addition, reported results in the remaining RCTs were inconsistent. The largest RCT showed that treatment using PRP compared with corticosteroid injection resulted in statistically significant improvement in pain and disability, but not quality of life. Larger RCTs are needed to address uncertainties regarding efficacy and safety.

In 2013, the National Institute for Health and Care Excellence (NICE) issued guidance on the use of autologous blood injection (with or without techniques for producing PRP) for plantar fasciitis. The guideline concluded that the evidence on autologous blood injection for plantar fasciitis raised no major safety concerns but that the evidence on efficacy was “inadequate in quantity and quality."

PRIMARY TREATMENT FOR OSTEOCHONDRAL LESIONS
The evidence base evaluating the use of PRP for the treatment of osteochondral lesions includes an open-labeled quasi-randomized study (Mei-Dan et al. 2012). No RCTs on the treatment of osteochondral lesions were identified. Relevant reported outcomes include symptoms, functional outcomes, health status measures, quality of life, and treatment-related morbidity. The quasi-randomized study found a statistically significant greater impact on outcomes in the PRP group than in the hyaluronic acid group. However, study limitations include lack of adequately randomized studies, lack of blinding, lack of sham controls, and comparison only to an intervention of uncertain efficacy. Adequately powered and blinded RCTs are required to confirm these findings. ​

PRIMARY TREATMENT FOR KNEE OR HIP OSTEOARTHRITIS
The evidence base evaluating the use of PRP in individuals with knee or hip osteoarthritis includes multiple RCTs (Knee: Cole BJ​ et al. 2017; Trueba Vasavilbaso C​ et al. 2017; Reyes-Sosa R et al. 2020; Elksnins-Finogejevs A​ et al. 2020 and Hip: Dallari D et al. 2016) and systematic reviews (Knee: Chang KV​ et al. 2014; Laudy AB et al. 2015; Lai LP et al. 2015; Meheux CJ et al. 2016; Xu Z​ et al. 2017; Johal H​ et al. 2019; Trams E et al. 2020 and Hip: Gazendam A et al. 2021). Relevant reported outcomes include symptoms, functional outcomes, health status measures, quality of life, and treatment-related morbidity. Most trials have compared PRP with hyaluronic acid for knee osteoarthritis. Systematic reviews have generally found that PRP was more effective than placebo or hyaluronic acid in reducing pain and improving function. However, the authors of these systematic reviews have noted that their findings should be interpreted with caution due to important limitations including significant residual statistical heterogeneity, questionable clinical significance, and high risk of bias in study conduct. RCTs with follow-up durations of at least 12 months published after the systematic reviews found statistically significant 12 month reductions in pain and function scores, but these findings were also limited by important study limitations including potential inadequate control for selection bias and limited or unclear blinding. In addition, the reductions were not maintained at 5 years. Furthmore, the use of hyaluronic acid as a comparator is questionable, because the evidence demonstrating the benefit of hyaluronic acid treatment for osteoarthritis is not robust. The single systematic review evaluating hip osteoarthritis did not report any statistically or clinically significant differences in pain or functional outcomes compared to corticosteroids or placebo. Additional larger controlled studies comparing PRP with placebo and alternatives other than hyaluronic acid are needed to determine the efficacy of PRP for knee and hip osteoarthritis. Further studies are also needed to determine the optimal protocol for delivering PRP. 

In 2013, the American Academy of Orthopaedic Surgeons (AAOS) guidelines did not recommend for or against growth factor injections and/or PRP for individuals with symptomatic osteoarthritis of the knee. The recommendation of inconclusive was based on a single low-quality study and conflicting findings. The AAOS recommendation was based on three studies published before May 2012.

In 2017, the AAOS issued evidence-based guidelines on the management of osteoarthritis of the hip. In the section on intra-articular injectables, the guidelines stated there is strong evidence supporting the use of intra-articular corticosteroids to improve function and reduce pain in the short term for individuals with osteoarthritis of the hip. There was also strong evidence that the use of intra-articular hyaluronic acid does not perform better than placebo in improving function, stiffness, and pain in patients with hip osteoarthritis. The guidelines also noted that there were no high-quality studies comparing PRP with placebo for the treatment of osteoarthritis of the hip.

In 2019, the National Institute for Health and Care Excellence (NICE)​ issued guidance on the use of PRP for knee osteoarthritis. The guideline concluded that current evidence on PRP for knee osteoarthritis raised “no major safety concerns”; however, the “evidence on efficacy is limited in quality." Therefore, NICE recommended that "this procedure should only be used with special arrangements for clinical governance, consent, and audit or research."

ADJUNCT TO SURGERY
Anterior Cruciate Ligament (ACL) Reconstruction

The evidence base evaluating the use of PRP in conjunction with ACL reconstruction surgery includes several systematic reviews (Moraes VY et al. 2013; Figueroa D et al 2015; Trams E et al. 2020) of multiple RCTs, quasi-randomized studies, and/or prospective studies. Relevant reported outcomes include symptoms, functional outcomes, health status measures, quality of life, morbid events, resource utilization, and treatment-related morbidity. Two systematic reviews conducted a meta-analysis, which showed that adjunctive PRP treatment did not result in a significant effect on International Knee Documentation Committee scores, a patient-reported, knee-specific outcome measure that assesses pain and functional activity. Individual studies have shown mixed results.

Hip Fracture​

The evidence base evaluating the use of PRP in individuals with hip fracture consists a single-blind, open-labeled RCT (Griffin XL et al. 2013). The primary outcome measure was the failure of fixation within 12 months, defined as any revision surgery. The overall risk of revision by 12 months was 36.9%, and the risk of death was 21.5%. There was no significant risk reduction (39.7% control vs. 34.1% PRP; absolute risk reduction, 5.6%; 95% CI, -10.6% to 21.8%) or significant difference between groups for most of the secondary outcome measures. For example, mortality was 23% in the control group and 20% in the PRP group. The length of stay was significantly reduced in the PRP treated group (median difference, 8 days). For this measure, there is a potential for bias from the nonblinded treating physician.​

Long Bone Nonunion

The evidence base evaluating the use of PRP in individuals with long bone nonunion includes three RCTs (Dallari D et al. 2007; Calori GM​ et al. 2008; Samuel G et al. 2018). Relevant reported outcomes include symptoms, functional outcomes, health status measures, quality of life, morbid events, resource utilization, and treatment-related morbidity. One RCT (Dallari D et al. 2007​) with a substantial risk of bias failed to show significant differences in patient-reported or clinician-assessed functional outcome scores between those who received PRP plus allogenic bone graft and those who received only allogenic bone graft. While the study showed a statistically significant increase in the proportion of bones that healed in individuals receiving PRP in a modified intention-to-treat analysis, the results did not differ in the intention-to-treat analysis. The second RCT (Calori GM​ et al. 2008), which compared PRP with recombinant human bone morphogenetic protein-7 (rhBMP-7), also failed to show any clinical or radiologic benefits of PRP over rhBMP-7. The third RCT (Samuel G et al. 2018) reported no difference in the number of unions or time to union in individuals receiving PRP versus no treatment.

Rotator Cuff Repair

The evidence base evaluating the use of PRP in individuals undergoing​ rotator cuff repair includes three RCTs (Walsh et al. 2018; Malavolta et al. 2018; Snow et al. 2019) and systematic reviews (Moraes et al. 2013; Zhao​ et al. 2015; Fu et al. 2017; Chen et al. 2018; ​Wang et al. 2019; Johal et al. 2019; Chen et al. 2020)​. Relevant reported outcomes include​ symptoms, functional outcomes, health status measures, quality of life, morbid events, resource utilization, and treatment-related morbidity. Although systematic reviews consistently found significant reductions in pain with PRP at 12 months, study limitations prevent interpretation of these findings. Furthermore, the pain reductions with PRP were not maintained in longer-term studies. Finally, the systematic reviews and meta-analyses failed to show a statistically and/or clinically significant impact on other outcomes.

Spinal Fusion

The evidence base evaluating the use of PRP in individuals undergoing spinal fusion consists of a single, small (N=62), unblinded, single-center RCT (Kubota et al. 2019) and two prospective observational studies (Carreon LY et al. 2005; Tsai CH et al. 2009)​. The RCT compared PRP to no PRP. Follow-up was 24 months. Although fusion rates were significantly improved with PRP, there were no significant differences in VAS scores (i.e., pain) between the two groups. Major limitations of this RCT include that individuals were unblinded to treatment and there was no placebo comparator. The two observational studies found no differences in fusion rates with use of a platelet gel or platelet glue compared with historical controls. 

Subacromial Decompression Surgery

The evidence base evaluating the use of PRP in individuals undergoing subacromial decompression surgery consists of a single, small (N=40), double-blinded RCT (Everts et al. 2008)​. Neither self-assessed nor physician-assessed instability improved. Both subjective pain and use of pain medication were lower in the PRP group across the six weeks of measurements. For example, at two weeks after surgery, VAS scores for pain were lower by about 50% in the PRP group, and only one (5%) individual in the PRP group was taking pain medication compared with 10 (50%) in the control group. Objective measures of range of motion showed clinically significant improvements in the PRP group across the six-week assessment period, with individuals reporting improvements in activities of daily living, such as the ability to sleep on the operated shoulder at four weeks after surgery and earlier return to work.​ Larger trials are required to confirm these results. 

Total Knee Arthroplasty

The evidence base evaluating the use of PRP in individuals undergoing​ total knee arthroplasty (TKA) consists of a single systematic review and meta-analysis that includes six RCTs (N=621) evaluating the effects of intraoperative PRP as an adjunct to TKA (Trams et al. 2020). Two studies were deemed at high risk of bias. The primary prupose of the studies was to assess blood loss during the procedure. While there were significant differences in favor of PRP in the overall effect on blood parameters in comparison to the untreated control groups, no significant differences in range of motion, functional outcomes, or long-term pain were observed.​

BLOOD-DERIVED PRODUCTS FOR CHRONIC NON-HEALING WOUNDS

Wound healing is a dynamic, interactive process that involves multiple cells and proteins. There are three progressive stages of normal wound healing, and the typical wound healing duration is about 4 weeks. Whereas a cutaneous wound is a disruption of the normal anatomic structure and function of the skin, a subcutaneous wound involves tissue below the skin's surface. Wounds are categorized as either acute (in which the normal wound healing stages are not yet completed but it is presumed they will be, resulting in orderly and timely wound repair) or chronic (in which a wound has failed to progress through the normal wound healing stages within a sufficient time period).

Platelet-rich plasma (PRP) is produced in an autologous or homologous manner. Autologous PRP is composed of blood from an individual who will ultimately receive the PRP. Alternatively, homologous PRP is derived from blood from multiple donors. In autologous PRP, blood is donated by the individual and centrifuged to produce an autologous gel for treatment of chronic, non-healing cutaneous wounds that persist for 30 days or longer and fail to properly complete the healing process. Autologous blood-derived products for chronic, non-healing wounds include both platelet-derived growth factor (PDGF) products such as Procuren®, and PRP products such as AutoloGel™. PRP is different from previous products in that it contains whole cells, including white cells, red cells, plasma, platelets, fibrin, stem cells, and fibrocyte precursors. PRP is used by physicians in clinical settings in treating chronic, non-healing wounds, open, cutaneous wounds, soft tissue and bone. Alternatively, PDGF does not contain cells and was previously marketed as a product to be used by patients at home.​

References

Ahmed M, Reffat SA, Hassan A, et al. Platelet-Rich Plasma for the Treatment of Clean Diabetic Foot Ulcers. Ann Vasc Surg. 2017;38:206-211.

Alamdari DH, Asadi M, Rahim AN, et al. Efficacy and Safety of Pleurodesis Using Platelet-Rich Plasma and Fibrin Glue in Management of Postoperative Chylothorax After Esophagectomy. World J Surg. 2018;42(4):1046-1055.

Almdahl SM, Veel T, Halvorsen P, et al. Randomized prospective trial of saphenous vein harvest site infection after wound closure with and without topical application of autologous platelet-rich plasma. Eur J Cardiothorac Surg. 2011;39(1):44-8.

American Academy of Orthopaedic Surgeons. Helping Fractures Heal (Orthobiologics). [OrthoInfo Web site]. 10/2020. Available at: https://www.orthoinfo.org/en/treatment/helping-fractures-heal-orthobiologics/. Accessed on February 14, 2022.

American Academy of Orthopaedic Surgeons. Management of Glenohumeral Joint Osteoarthritis Evidence-Based Clinical Practice Guideline. [AAOS Web site]. March 23, 2020. Available at: https://www.aaos.org/globalassets/quality-and-practice-resources/glenohumeral/gjo-cpg.pdf. Accessed on February 16, 2022.

American Academy of Orthopaedic Surgeons. Management of Osteoarthritis of the Hip: Evidence-Based Clinical Practice Guideline. [AAOS Web site]. March 13, 2017. Available at:  https://www.aaos.org/globalassets/quality-and-practice-resources/osteoarthritis-of-the-hip/oa-hip-cpg_6-11-19.pdf. Accessed on February 17, 2022.​

American Academy of Orthopaedic Surgeons. Treatment of Osteoarthritis of the Knee - 2nd Edition. [AAOS Web site]. May 18, 2013. Available at: https://www.aaos.org/globalassets/quality-and-practice-resources/osteoarthritis-of-the-knee/osteoarthritis-of-the-knee-2nd-editiion-clinical-practice-guideline.pdf. Accessed on February 17, 2022.

Andia I, Latorre PM, Gomez MC, et al. Platelet-rich plasma in the conservative treatment of painful tendinopathy: a systematic review and meta-analysis of controlled studies. Br Med Bull. 2014;110(1):99-115.

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Tsikopoulos K, Tsikopoulos I, Simeonidis E, et al. The clinical impact of platelet-rich plasma on tendinopathy compared to placebo or dry needling injections: A meta-analysis. Phys Ther Sport. 2016;17:87-94.

US Food and Drug Administration (FDA). 510(k) summary: Magellan™ Autologous Platelet Separator System. [FDA Web site]. 08/12/2002. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf2/K021902.pdf. Accessed on February 15, 2022.

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US Food and Drug Administration (FDA). REGRANEX (becaplermin) gel. [FDA Web site]. 11/2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/103691s5134lbl.pdf​. Accessed on February 15, 2022​.

US Food and Drug Administration (FDA). Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use. July 2020. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/regulatory-considerations-human-cells-tissues-and-cellular-and-tissue-based-products-minimal. Accessed on February 16, 2022.

Vangsness CT, Farr J, Boyd J, et al. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J Bone Joint Surg Am. 2014;96(2):90-8.

Vanichkachorn J, Peppers T, Bullard D, et al. A prospective clinical and radiographic 12-month outcome study of patients undergoing single-level anterior cervical discectomy and fusion for symptomatic cervical degenerative disc disease utilizing a novel viable allogeneic, cancellous, bone matrix (trinity evolution) with a comparison to historical controls. Eur Spine J. 2016;25(7):2233-8.

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Yeung CY, Hsieh PS, Wei LG, et al. Efficacy of Lyophilised Platelet-Rich Plasma Powder on Healing Rate in Patients With Deep Second Degree Burn Injury: A Prospective Double-Blind Randomized Clinical Trial. Ann Plast Surg. 2018;80(2S Suppl 1):S66-S69.​

Zhang L Qiang D, Sun YH. Clinical observation of autologous platelet rich gel in the treatment of diabetic foot ulcers. Ningxia Med J. 2016;38:809-811.

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Zhao XH, Gu HF, Xu ZR, et al. Efficacy of topical recombinant human platelet-derived growth factor for treatment of diabetic lower-extremity ulcers: Systematic review and meta-analysis. Metabolism. 2014;63(10):1304-13.

Zhou SF, Estrera AL, Loubser P, et al. Autologous platelet-rich plasma reduces transfusions during ascending aortic arch repair: a prospective, randomized, controlled trial. Ann Thorac Surg. 2015;99(4):1282-90.

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Coding

CPT Procedure Code Number(s)
EXPERIMENTAL/INVESTIGATIONAL

0232T, 0481T, 0565T, 0566T

THE FOLLOWING CPT CODES ARE NOT SPECIFIC TO THE SERVICE(S) DESCRIBED WITHIN THIS POLICY. WHEN USED TO REPRESENT STEM-CELL THERAPY FOR ORTHOPEDIC APPLICATIONS THESE CODES ARE CONSIDERED EXPERIMENTAL/INVESTIGATIONAL.

0263T, 0264T, 0265T, 38205, 38206, 38230, 38232, 38240, 38241​
ICD - 10 Procedure Code Number(s)
N/A
ICD - 10 Diagnosis Code Number(s)
N/A
HCPCS Level II Code Number(s)
MEDICALLY NECESSARY
​
G0465 Autologous platelet rich plasma (PRP) for diabetic chronic wounds/ulcers, using an FDA-cleared device (includes administration, dressings, phlebotomy, centrifugation, and all other preparatory procedures, per treatment)

EXPERIMENTAL/INVESTIGATIONAL

G0460 Autologous platelet rich plasma for non-diabetic chronic wounds/ulcers, including phlebotomy, centrifugation, and all other preparatory procedures, administration and dressings, per treatment​

S9055 Procuren or other growth factor preparation to promote wound healing

WHEN USED TO REPRESENT STEM-CELL THERAPY FOR ORTHOPEDIC APPLICATIONS THESE CODES ARE CONSIDERED EXPERIMENTAL/INVESTIGATIONAL.

S2150 Bone marrow or blood-derived stem cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; including: pheresis and cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitalization with outpatient follow-up; medical/surgical, diagnostic, emergency, and rehabilitative services; and the number of days of pre- and posttransplant care in the global definition

Revenue Code Number(s)
N/A


Coding and Billing Requirements

Inclusion of a code in this policy does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

To report platelet-rich plasma (PRP) injections, professional providers must use CPT 0232T.

Policy History

7/11/2022
7/11/2022
MA07.008
Medical Policy Bulletin
Medicare Advantage
No
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